This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. B. Research Experience Proposed for COBRE Grant Application Systemic lupus erythematosus (SLE) is a complex, chronic and only partially-understood autoimmune disorder with multiple organ involvement. Genetic origins for SLE are supported by high heritability (66%), familial aggregation, increased monozygotic twin concordance, genetic linkages, and candidate gene genetic association, including HLA alleles, Fc receptors, and complement components. Relevant environmental factors likely include infections, therapeutics, personal habits (smoking), and diet. This study explores genetic associations of the disease with the following specific aims: Specific Aim 1: Use DNA pooling techniques to identify non-coding region SNPs that are associated with SLE in a European-American (EA) population. Specific Aim 2: Conduct multiple fine-mapping experiments of the regions identified in Aim 1 using at least two genotyping platforms to characterize the individual associated SNPs. Specific Aim 3: Conduct expression and structural analysis on a "risk" and "non-risk" haplotype identified in Aim 2 as part of functional studies.